Berman shape 05 fin
Download as PPT, PDF0 likes368 views
SPECT/CT shows promise for atherosclerosis imaging by combining anatomical CT imaging of plaque volume with molecular SPECT imaging of plaque activity. SPECT could potentially image multiple molecular processes simultaneously, such as apoptosis, oxidized LDL, or inflammation. Recent advances in SPECT technology include improved resolution, sensitivity, and the ability to perform dynamic cardiac SPECT to quantify blood flow and endothelial function. Combined structural and molecular imaging may allow more accurate risk assessment and monitoring of treatment response than anatomical methods alone. However, further developments are still needed, including new tracers approved for human use.
Berman shape 05 fin
- 1. SPECT/CT for Atherosclerosis Imaging: The Future is Clear Daniel S. Berman, MD Director, Cardiac Imaging Cedars-Sinai Medical Center Professor of Medicine David Geffen School of Medicine at UCLA
- 2. DISCLOSURE Daniel S. Berman, M.D. declares the following relationships: Grant Support: BMS Medical Imaging, Astellas, GE Amersham, Mallinckrodt-Tyco Speakers Bureau: Astellas Consultant: Mallinckrodt-Tyco Spectrum Dynamics Royalties: Cedars-Sinai Medical Center Stockholder: Spectrum Dynamics
- 3. MDCT Technical Parameters 2005 Four major manufacturers with 64 slice CT • ~.4-.5 mm3 isotropic voxels • Temporal resolution: 165-210 ms for 180° (330-420 ms rotation time) • Cardiac study in 5-10 beats
- 4. 76 M #3311-1526 Sx: ASYMPTOMATIC RISK FACTORS: ↑CHOLESTEROL RESTING ECG: NORMAL RESULTS OF EXERCISE: DURATION: 9:39 HR: 131 (91% MPHR) BP: 134/74 → 150/72 CLINICAL RESPONSE: NONISCHEMIC ECG RESPONSE: NONISCHEMIC
- 5. 73 M #3311-1526 EBT RESULTS Location # Calcified Lesions Calcified Plaque Volume (mm 3 ) Calcium Score LAD 3 97 126 * 32th percentile
- 7. 76 M 11/3/05 #3311-1526 Stress MIBI Rest Tl Stress MIBI Rest Tl Stress MIBI Rest Tl Stress MIBI Rest Tl
- 9. A B C D Calcification Soft Plaque D2 Lesion 76 M #3311-1526
- 10. Limitations of Anatomic Imaging Little information regarding disease activity • Two patients: with mild coronary calcium, score ~100 discovered on screening 1 yr ago and placed on statin, ASA, and ACE • Patient A: recently symptomatic • Patient B: still asymptomatic • Both undergo CT coronary angiography, and are found to have 75% mid LAD stenosis by CT angio AND extensive non-calcified plaque by IVUS • Should the treatment be the same?
- 11. It will be!
- 12. Why not catheterize all suspected CAD patients? Occulo-stenotic reflex*: unnecessary PCI• Immediate Risk – Death (rare) – Clinical MI (uncommon) – Subclinical MI (more frequent) – Branch occlusion (frequent) • Late risk – Possible higher mortality risk than medical therapy in patients without ischemia • Costs • Objective measurements of perfusion and function • Accurate for assessing risk of cardiac death (CD) • Relationship of degree of abnormality to risk • Identifies likely to benefit from revascularization • Proven as cost effective “gatekeeper” to the cath lab Limitations • Cannot detect early atherosclerosis • May underestimate extent of CAD *Topol
- 13. Cardiac CT Limitations • Densely calcified plaques: nondiagnostic • Dependence on low HR and regular rhythm • Radiation, iodinated contrast • Overestimation of stenosis • No information regarding plaque “activity”
- 14. • No Hx CAD • Known CAD • Post-PTCA • Post-CABG • Men and Women • Sx and Asx • DM • Elderly SPECT: Risk Increases as a Function of Stress Perfusion Abnormality Extent/Severity of Perfusion Defec Risk* *Adjusted or unadjusted Guidelines for Clinical Use of Cardiac Radionuclide Imaging 2003 Data from over 50,000 patients
- 15. logHazardRatio 0123456 % Myocardium Ischemic 0 12.5% 25% 32.5% 50% Medical Rx Revasc * * *p<0.001 Adjusted† Risk of Cardiac Death vs MPS ischemia Revascularization vs Medical Rx Hachamovitch, et al Circulation 2003 † Adjusted for predictors of revascularization as well as clinical, hx, stress SPECT data
- 16. VISUAL SSS STANDARD TPD stenosis ≥ 50% 1.00.75.50.250.00 1.00 .75 .50 .25 0.00 1 - Specificity Sensitivity Changes in Analytic Software Automatic Total Perfusion Deficit ** * P < 0.05 Slomka, et al J Nucl Cardiol 2005;12:66-77
- 17. When was the last fundamental change in the detector technology? Nuclear Cardiology: Single Photon Imaging
- 18. When was the last fundamental change in the detector technology? 1958: Hal Anger patented the current NaI (Tl) detector/photomultiplier array configuration (#3011057) Nuclear Cardiology: Single Photon Imaging
- 19. Resolution & Contrast - a Comparison Total counts: 2,500K Total counts: 2,500K Spectrum-Dynamics Coronal Sagittal Transverse Net acquisition time: 9 minutes Frame angle: 3°, positions:60, 9sec per position Net acquisition time: 1 minute positions:40, 1.5sec per position Millennium VG a Spectrum Dynamics Measured Contrast Target A: 1.6 Target B: 2.2 Millenium Measured Contrast Target A: unseen 3:1 2:1
- 20. Cardiac Phantom Conventional • No AC • Acquisition time 12.5 m Spectrum Dynamics • No AC • Acquisition time 1.25 m •Tc99m •Heart : .5mCi •Background : 2mCi (.19mCi/l) •Liver : .23mCi (.19mCi/liter)
- 21. Cardiac SPECT Improvements Implications for CHD and Atherosclerosis Testing • Increased sensitivity: reduced acquisition time – Dynamic cardiac SPECT: • time-activity curves for blood and myocardium • Compartment modeling results in: – Absolute blood flow (voxel) – Coronary Flow Reserve: a region compared to itself – Coronary endothelial function (CPT) • Increased resolution: – Potential to directly image plaque • quantify “activity” of atherosclerosis
- 22. SPECT/CT Philips Precedence Siemens Simbia
- 23. Dynamic SPECT for Molecular Imaging • Noninvasive biopsy • Specific diagnosis CT for Structure DynaQ™ hybrid scanner
- 24. Who needs PET/CT or SPECT/CT • Equivocal nuclear • Follow-up studies after initial CT (or nuclear) • Why simultaneous: molecular imaging
- 25. Comparative Spatial Resolution and Tracer Concentration SPECT PET ECHO MRI CT Resolution (mm) 7-15 3-10 < 1 < 1 < 1 Tracer Concentration pM-nM* pM-nM* 10-100 μM 10-100 μM 10-100 μM *picomolar-nanomolar concentrations employed are key advantage of the radionuclide methods
- 26. translocase death domains mediated signaling activation of the executioner of apoptosis scramblase floppase ? binding followed by 2D-crystallization Annexin V Detection of the apoptotic cell TNF or Fas Ligand TNFR or CD95 + +- Courtesy Chris Reutlingsperger, Maastricht University Tc-99m Annexin V: Probe for Vulnerable Plaque
- 27. Old TIA Recent TIA A B C D Transverse Coronal ANT L Annexin IHC in Endarterectomy Keitselaar, Hofstra, Narula; NEJM 2004 Annexin-V Imaging For ApoptosisAnnexin-V Imaging For Apoptosis
- 28. Annexin V-Tc99m autoradiograph Digital photograph dissected apoE-/- aorta H & E Histological AHA classification Stage IVa (vulnerable plaque) Tc-99m Annexin dissected aorta apoE -/- mouse C. Mori Stanford, 2005
- 29. 99m Tc-Annexin V SPECT for In Vivo Detection of Atherosclerotic Lesions in Porcine Coronary Arteries Johnson et al. J Nucl Med 2005;46:1186-93 Scan positive Scan negative
- 30. Imaging of Atherosclerotic Plaques Using a Human Antibody Against the Extra-Domain B of Fibronectin Matter et al. Circ Res 2004;95:1225-33 125 I-labeled L19 to atherosclerotic plaques in ApoE-/- mice.
- 31. OxLDL AB uptake reflects plaque burden R=0.95 P<0.001 0.00 0.05 0.10 0.15 0.20 0.25 0 500 1000 1500 2000 Aortic weight (mg) (%ID) MDA2 125 I-MDA2 Uptake in Mouse and Rabbit Atherosclerotic Plaques Tsimikas J Nucl Cardiol 1999, ATVB 2001
- 32. IL2 SPECT in 2 pts with bi-lateral carotid plaques A Annovazzi e A Signore ACC 2005
- 33. IL2 SPECT: Carotid T/B ratios in patients from LS before and after 3 month treatment 1 1,5 2 2,5 3 3,5 Before therapy After therapy 99mTc-IL2uptake(C/Bratios) Atorvastatin 1 1,5 2 2,5 3 3,5 Before diet After diet Hypocholesterolemic diet
- 34. SPECT for imaging vulnerable plaque Potential to Image Multiple Molecular Processes Simulaneously • Apoptosis • IK-17 • Oxidized LDL • Interleukin 2 • Thrombus • Activated platelets • Neovascularization
- 35. Molecular Imaging Needed Developments • Discovery in molecular biology • New probes (with FDA approval) • Multimodality technology – Structure/function Post-processing software • Reimbursement
- 36. SPECT/CT for Atherosclerosis Imaging • CT: quantify plaque volume • SPECT or PET: – quantify plaque activity – Potential to quantify rest/stress blood flow Advantage of SPECT • Multiple tracers simlutaneously • Possible wider availability of tracers and cameras • Potential of SPECT • Increased sensitivity and resolution need to be realized